Microfluidic devices control and manipulate fluid flows with length scales less than about one millimeter and fluid volumes of less than about a microliter. Microfluidic systems are now in widespread use for a host of applications including biochemical analysis, drug screening, biosensors, chemical reactions, cell sorting, sequencing of nucleic acids, and transport of small volumes of materials. Many of these applications require efficient mixing of biological materials and chemical reagents for the necessary reactions to occur. For these applications, rapid homogenization of two fluid streams in a minimal amount of space is generally highly desirable.
When the dimensions are several hundred micrometers or less, pressure flows are laminar and uniaxial. The Reynolds number (i.e., the ratio of inertial to viscous forces) is small, on the order of unity, and mixing is purely diffusive. For this reason, a molecular diffusion-based mixing process can take tens of seconds up to several minutes. Moreover, the mixing time in solutions containing complex biomolecules, or other large particles, can increase to hours as compared to simple proteins. Even at the scale of microchannels, diffusion-based mixing is slow compared to convection of material along the channel, as described by the Peclet number (i.e., the ratio of convective to diffusive transport, typically greater than one hundred). For example, in water flowing at a velocity of about 1 cm/sec in a 100-μm-wide channel, mixing lengths can be up to tens of centimeters. These mixing times and lengths are far too long for practical, portable microfluidic systems, especially when large particles are to be mixed.
To improve mixing efficacy and homogenization of fluid streams in a microchannel, rapid folding and stretching of the fluid is essential to reduce the mixing time. Rapid stretching and folding of the fluid can be accomplished by using passive or active mixing methods. Passive micromixers rely on forcing liquids through static geometries to fold and stretch the fluid, thereby increasing the interfacial area between adjacent fluid streams. Multiple stage laminations and flow splitting have been used to increase dramatically the interfacial area. See J. Branebjerg et al., “Fast mixing by lamination,” Proc. IEEE MEMS Workshop, San Diego, Calif. (1996); and N. Schwesinger et al., “A modular microfluid system with an integrated micromixer,” J. Micromech. Microeng. 6, 99 (1996). Recently, chaotic advection using complicated three-dimensional serpentine twisted channels has been used to achieve seemingly random and chaotic particle trajectories within fluid channels. See R. H. Liu et al., “Passive mixing in a three-dimensional serpentine microchannel,” J. Microelectromech. Sys. 9, 190 (2000); D. J. Beebe et al., “Passive mixing in microchannels: Fabrication and flow experiments,” Mec. Ind. 2, 343 (2001); and R. A. Vijayendran et al., “Evaluation of a three-dimensional micromixer in a surface-based biosensor,” Langmuir 19, 1824 (2003). However, to date such passive micromixers lack efficiency at low Reynolds number. More recently, a passive micromixer using bas-relief features has been demonstrated to provide efficacious mixing, even at low Reynolds number. See A. D. Stroock et al., “Chaotic mixer for microchannels,” Science 295, 647 (2002). The bas-relief structure was used to generate transverse flows in the microchannel such that liquid streams twisted over one another. However, a significant disadvantage is that, in order to generate the chaotic-advection required for mixing, complex three-dimensional microstructures must be fabricated. Further, these meandering paths and complex flow structures can generate dead volume. Such dead volumes can cause sample loss, decreased throughput, increased detection time, and can easily foul when using complex solutions. Moreover, passive mixing methods require fluid flow for mixing to occur.
Active micromixers rely on internal mixing forces within a fluid-carrying channel, typically using moving parts. Active micromixers can be driven, for example, by pressure, temperature, electrohydrodynamic, dielectrophoretic, electrokinetic, magnetohydrodynamic, or ultrasonic actuators. Active micromixers can have greater mixing efficacy than passive micromixers, especially for flows at low Reynolds number. Further, the mixing can be switched on and off, as desired, and can be done in the absence of fluid flow. This assures that the chemical reaction time is faster than the residence time in the microchannel. However, active micromixers require an external power source, and the integration of active mixers in microfluidic systems can also be challenging, requiring complicated actuation structures and costly and complex fabrication processes.
It is well known that ultrasonic actuation can significantly influence the pressure variation within fluids. Acoustic pressure variation can be large enough to cause cavitation, where the pressure forces exceed the intermolecular cohesion forces. Though bubble formation and collapse can induce mixing, a secondary mechanism exists when the acoustic energy is dissipated by viscous stress. The nonlinear hydrodynamic coupling of high amplitude sound waves with the dissipative fluid medium creates an acoustic pressure gradient within the fluid. This large nonlinear gradient results in a steady fluid flow, in a process known as “quartz wind” or acoustic streaming.
Active micromixers based on acoustic streaming have produced liquid oscillations using thickness-mode resonances in zinc oxide (ZnO), induced ultrasonic vibration of thin silicon membranes to actively mix fluids using lead-zirconate-titanate (PZT), and moved liquid droplets using 128° Y-cut X-propagating lithium niobate (128° YX LiNbO3). Typically, these micromixers use transducer disks attached to the exterior of a fluidic channel to convert radio-frequency electrical energy into an ultrasonic acoustic wave normal to the disk. See X. Zhu and E. S. Kim, “Microfluidic motion generation with acoustic waves,” Sensors and Actuators A 66, 355 (1998); Z. Yang et al., “Ultrasonic micromixer for microfluidic systems,” Sensors and Actuators A 93, 266 (2001); and G. G. Yaralioglu et al., “Ultrasonic Mixing in Microfluidic Channels Using Integrated Transducers,” Anal. Chem. 76, 3694 (2004).
Acoustic streaming can also be generated by a surface acoustic wave (SAW) device. A Rayleigh wave can readily radiate longitudinal waves into a fluid when the SAW propagation surface is in contact with the fluid. The SAW streaming force resulting from a leaky Rayleigh wave can be much greater than other types of acoustic streaming forces, such as attenuated plane waves traveling in a bulk liquid. However, early studies, that used 128° YX LiNbO3 to perturb fluids, only considered acoustic wave streaming in open systems and did not use the streaming force for fluid mixing in closed channels. See T. Uchida et al., “Investigation of Acoustic Streaming Excited by Surface Acoustic Waves,” Proc. 1995 IEEE Ultrasonics Symposium, 1081 (1995); K. Miyamoto et al., “Nonlinear vibration of liquid droplets by surface acoustic wave excitation,” Jpn. J. Appl. Phys. 41, 3465 (2002); and S. Shiokawa and Y. Matsui, “The Dynamics of SAW Streaming and its Application to Fluid Devices,” Mat. Res. Soc. Symp. Proc. 360, 53 (1995), all of which are incorporated herein by reference.
Therefore, a need still exists for an efficient, active micromixer based on SAW streaming that can be integrated in a closed microfluidic system.